Effects of nanopillar array diameter and spacing on cancer cell capture and cell behaviors.

While substrates with nanopillars (NPs) have emerged as promising platforms for isolation of circulating tumor cells (CTCs), the influence of diameter and spacing of NPs on CTC capture is still unclear. In this paper, CTC-capture yield and cell behaviors have been investigated by using antibody functionalized NPs of various diameters (120-1100 nm) and spacings (35-800 nm). The results show a linear relationship between the cell capture yield and effective contact area of NP substrates where a NP array of small diameter and reasonable spacing is preferred; however, spacing that is too small or too large adversely impairs the capture efficiency and specificity, respectively. In addition, the formation of pseudopodia between captured cells and the substrate is found to be dependent not only on cell adhesion status but also on elution strength and shear direction. These findings provide essential guidance in designing NP substrates for more efficient capture of CTCs and manipulation of cytomorphology in future.

[1]  Chwee Teck Lim,et al.  Versatile label free biochip for the detection of circulating tumor cells from peripheral blood in cancer patients. , 2010, Biosensors & bioelectronics.

[2]  A. Grichine,et al.  Lamellipodia nucleation by filopodia depends on integrin occupancy and downstream Rac1 signaling. , 2008, Experimental cell research.

[3]  J. Gilchrist,et al.  Effect of surface nanotopography on immunoaffinity cell capture in microfluidic devices. , 2011, Langmuir : the ACS journal of surfaces and colloids.

[4]  Andrew D Ellington,et al.  Nanotextured substrates with immobilized aptamers for cancer cell isolation and cytology , 2012, Cancer.

[5]  Mukti Aryal,et al.  Inhibited cell spreading on polystyrene nanopillars fabricated by nanoimprinting and in situ elongation , 2010, Nanotechnology.

[6]  R. Rosenfeld.  Nature , 2009, Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery.

[7]  R. Jaccodine,et al.  Measurement of Strains at Si‐SiO2 Interface , 1966 .

[8]  Michael P. Sheetz,et al.  The relationship between force and focal complex development , 2002, The Journal of cell biology.

[9]  Daniel F. Hayes,et al.  Sensitive capture of circulating tumour cells by functionalised graphene oxide nanosheets , 2013, Nature nanotechnology.

[10]  Ho-Young Kim,et al.  Nanoscale patterning of microtextured surfaces to control superhydrophobic robustness. , 2010, Langmuir : the ACS journal of surfaces and colloids.

[11]  Sang‐Kwon Lee,et al.  Cell adhesion and migration on nanopatterned substrates and their effects on cell-capture yield , 2012, Nanotechnology.

[12]  Steven A. Soper,et al.  Separation of breast cancer cells from peripherally circulating blood using antibodies fixed in microchannels , 2004, SPIE BiOS.

[13]  Lei Jiang,et al.  Bio-inspired soft polystyrene nanotube substrate for rapid and highly efficient breast cancer-cell capture , 2013 .

[14]  M. King,et al.  Nanostructured Surfaces to Target and Kill Circulating Tumor Cells While Repelling Leukocytes. , 2012, Journal of nanomaterials.

[15]  Hyun Woo Shim,et al.  Electrochemical performance of Nixx , 2012 .

[16]  Andrew D. Ellington,et al.  Surface-immobilized aptamers for cancer cell isolation and microscopic cytology. , 2010, Cancer research.

[17]  Mengsu Yang,et al.  Cell adhesion and spreading behavior on vertically aligned silicon nanowire arrays. , 2009, ACS applied materials & interfaces.

[18]  Feng Zhang,et al.  Nanoroughened surfaces for efficient capture of circulating tumor cells without using capture antibodies. , 2013, ACS nano.

[19]  S. Digumarthy,et al.  Isolation of rare circulating tumour cells in cancer patients by microchip technology , 2007, Nature.

[20]  Max S Wicha,et al.  Circulating tumor cells: not all detected cells are bad and not all bad cells are detected. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[21]  K. Schütze,et al.  Isolation by size of epithelial tumor cells : a new method for the immunomorphological and molecular characterization of circulatingtumor cells. , 2000, The American journal of pathology.

[22]  Hartmut S. Leipner,et al.  Model for the Mass Transport during Metal-Assisted Chemical Etching with Contiguous Metal Films As Catalysts , 2012 .

[23]  Yu Song,et al.  Biospecies Capture and Detection at Low Concentration , 2012 .

[24]  Jaap M. J. den Toonder,et al.  Circulating tumor cells: the Grand Challenge. , 2011, Lab on a chip.

[25]  M. Mooseker,et al.  Organization of an actin filament-membrane complex. Filament polarity and membrane attachment in the microvilli of intestinal epithelial cells , 1975, The Journal of cell biology.

[26]  Lei Jiang,et al.  Programmable Fractal Nanostructured Interfaces for Specific Recognition and Electrochemical Release of Cancer Cells , 2013, Advanced materials.

[27]  M. Abercrombie,et al.  The Croonian Lecture, 1978 - The crawling movement of metazoan cells , 1980, Proceedings of the Royal Society of London. Series B. Biological Sciences.

[28]  Kinam Kim,et al.  Full surface embedding of gold clusters on silicon nanowires for efficient capture and photothermal therapy of circulating tumor cells. , 2012, Nano letters.

[29]  Hsian-Rong Tseng,et al.  Functionalized Conducting Polymer Nanodots for Enhanced Cell Capturing: The Synergistic Effect of Capture Agents and Nanostructures , 2011, Advanced materials.

[30]  D. Hammer,et al.  A semianalytic model of leukocyte rolling. , 2004, Biophysical journal.

[31]  U. Pal,et al.  Effects of crystallization and dopant concentration on the emission behavior of TiO2:Eu nanophosphors , 2012, Nanoscale Research Letters.

[32]  Robert Rosenberg,et al.  Detection of circulating tumor cells in blood using an optimized density gradient centrifugation. , 2003, Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer.

[33]  Yi-Kuen Lee,et al.  Highly efficient capture of circulating tumor cells by using nanostructured silicon substrates with integrated chaotic micromixers. , 2011, Angewandte Chemie.

[34]  Ruud H. Brakenhoff,et al.  Detection, clinical relevance and specific biological properties of disseminating tumour cells , 2008, Nature Reviews Cancer.

[35]  Yu Wang,et al.  Three‐Dimensional Graphene Composite Macroscopic Structures for Capture of Cancer Cells , 2014 .

[36]  Melanie Grunwald,et al.  Blood , 2011, The Lancet.

[37]  Kang Sun,et al.  Hydrophobic Interaction‐Mediated Capture and Release of Cancer Cells on Thermoresponsive Nanostructured Surfaces , 2013, Advanced materials.

[38]  K. Isselbacher,et al.  Isolation of circulating tumor cells using a microvortex-generating herringbone-chip , 2010, Proceedings of the National Academy of Sciences.

[39]  Waseem Asghar,et al.  Velocity effect on aptamer-based circulating tumor cell isolation in microfluidic devices. , 2011, The journal of physical chemistry. B.

[40]  Shutao Wang,et al.  Three-dimensional nano-biointerface as a new platform for guiding cell fate. , 2014, Chemical Society reviews.

[41]  Jason P. Gleghorn,et al.  Rare Cell Capture in Microfluidic Devices. , 2011, Chemical engineering science.

[42]  Weian Zhao,et al.  Bioinspired multivalent DNA network for capture and release of cells , 2012, Proceedings of the National Academy of Sciences.

[43]  Utkan Demirci,et al.  Nanostructured substrates for isolation of circulating tumor cells. , 2013, Nano today.

[44]  C. Fan,et al.  Silicon nanomaterials platform for bioimaging, biosensing, and cancer therapy. , 2014, Accounts of chemical research.